Research abstract

Letter abstract

Nature Biotechnology 23, 879 - 884 (2005)
Published online: 19 June 2005 | doi:10.1038/nbt1109

Engineering vascularized skeletal muscle tissue

Shulamit Levenberg1,2, Jeroen Rouwkema3, Mara Macdonald2, Evan S Garfein4, Daniel S Kohane5, Diane C Darland6, Robert Marini7, Clemens A van Blitterswijk3, Richard C Mulligan8, Patricia A D'Amore6 & Robert Langer2


One of the major obstacles in engineering thick, complex tissues such as muscle is the need to vascularize the tissue in vitro. Vascularization in vitro could maintain cell viability during tissue growth, induce structural organization and promote vascularization upon implantation. Here we describe the induction of endothelial vessel networks in engineered skeletal muscle tissue constructs using a three-dimensional multiculture system consisting of myoblasts, embryonic fibroblasts and endothelial cells coseeded on highly porous, biodegradable polymer scaffolds. Analysis of the conditions for induction and stabilization of the vessels in vitro showed that addition of embryonic fibroblasts increased the levels of vascular endothelial growth factor expression in the construct and promoted formation and stabilization of the endothelial vessels. We studied the survival and vascularization of the engineered muscle implants in vivo in three different models. Prevascularization improved the vascularization, blood perfusion and survival of the muscle tissue constructs after transplantation.

  1. Department of Biomedical Engineering, Technion 32000, Haifa, Israel.
  2. Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
  3. Institute for Biomedical Technology, Twente University, Prof. Bronkhorstlaan 10-D, Bilthoven, 3723MB, The Netherlands.
  4. Department of Surgery, Brigham and Women's Hospital, 75 Francis St., 02115, Boston, Massachusetts, USA.
  5. Department of Pediatrics, Massachusetts General Hospital, 55 Fruit St., 02114, Boston, Massachusetts, USA.
  6. The Schepens Eye Research Institute and Department of Ophthalmology 20 Staniford St., 02114, Boston, Massachusetts, USA.
  7. Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
  8. Department of Molecular Medicine, Children's Hospital 300 Longwood Avenue, 02115, Harvard Medical School, Boston, Massachusetts, USA.

Correspondence to: Robert Langer2 e-mail:

Correspondence to: Shulamit Levenberg1,2 e-mail:


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